The biological significance of DNA content

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Protein coding sequences in the human genome number only ~25,000 and constitute less than 2% of the total DNA content. The biological significance of the vast non-coding majority of the genome has remained enigmatic. Today, major initiatives involving sequence comparisons (e.g., ENCODE) are underway to determine whether and in what way portions of so-called "junk DNA" may be functional in regulatory or other capacities. More broadly, it has been known for more than 50 years that total genomic DNA content is non-neutral with respect to organism phenotypes. Indeed, genome size has been reported to correlate with a variety of traits in animals and plants, including body size, metabolic rate, and developmental rate. These relationships are thought to derive from causal links between genome size, cell size, and cell division rate, but to date this has not been addressed in detail. The research proposed here will bring modern technologies to bear on this long-standing question, and will focus on three different but interrelated study systems. The first involves comparisons of genome sizes and cell sizes from a diverse array of tissues and taxa in order to assess the universality of the genome size-cell size relationship. This will be accompanied by experimental work aimed at testing mechanistic hypotheses linking genome size to cell size via influences on cell cycle regulation. The second includes a study of vertebrates whose red blood cells contain no nuclei, but among whom the effects of DNA content on cell size persist. The third will examine the basis and consequences of the massive genome multiplication that occurs within certain arthropod tissues. In total, these three studies will allow several critical questions in large-scale genomics to be answered for the first time, and will contribute directly to my long-term goal of understanding the origins, characteristics, and biological relevance of non-coding DNA within animal genomes. This program will generate both data and methods of practical significance to biologists working in a range of biological disciplines, in addition to providing exceptional opportunities for student training.